Optical coherence tomography (OCT) is an optical imaging technology for performing in situ real-time cross-sectional imaging of tissue structures at a resolution of less than 10 microns. OCT measures the scattering profile of a sample along the OCT beam. Each scattering profile is called an axial scan, or A-scan. Cross-sectional images, called B-scans, and by extension 3D volumes, are built up from many A-scans, with the OCT beam moved to a set of transverse locations on the sample.
In recent years, it has been demonstrated that Fourier domain OCT (FD-OCT) has advantages over the original time-domain OCT (TD-OCT) (R. A. Leitgeb et al., “Performance of fourier domain vs. time domain optical coherence tomography,” Optics Express 11(8): 889-94 (2003); J. F. de Boer et al., “Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography,” Optics Letters 28(21): 2067-69 (2003); M. A. Choma et al., “Sensitivity advantage of swept source and Fourier domain optical coherence tomography,” Optics Express 11(18): 2183-89 (2003)). In TD-OCT, the optical path length between the sample and reference arms needs to be mechanically scanned. In FD-OCT, on the other hand, the optical path length difference between the sample and reference arm is not mechanically scanned. Instead, a full A-scan is obtained in parallel for all points along the sample axial line within a short time, determined by the wavelength sweep rate of a swept source in swept-source OCT (SS-OCT) or the line scan rate of the line scan camera in spectral-domain OCT (SD-OCT). As a result, the speed for each axial scan can be substantially increased as compared to the mechanical scanning speed of TD-OCT.
The spectral interferogram acquired through FD-OCT encodes the longitudinal sample structure at the focal spot. To recover the sample structure, the interference pattern can be inverse Fourier transformed. The inverse Fourier transform yields three components: the DC component, cross-correlation component, and auto-correlation component. The DC terms are often the largest component and are pathlength-independent. The cross-correlation terms contain the information of interest—the sample reflectivity profile. The auto-correlation terms represent interference between the different reflectors within the sample. Elements of all three of these components can lead to artifacts that can cause problems in data interpretation or processing.
In OCT signal processing, DC terms are normally suppressed by performing a processing step known as background subtraction. However, due to temporal variations in the detected power levels, the DC terms are often not fully subtracted. One artifact, the central line artifact, results due to the residual DC terms. This artifact manifests as a bright central line that could be several pixels thick and is near the zero optical delay position. The bright line artifact due to the residual DC terms can overwhelm the overlapping information of interest in the cross-correlation component.
Another artifact is the complex conjugate artifact, which arises from the cross-correlation terms. The complex conjugate artifact is a mirror image of the true image that appears on the opposite side of the zero-delay position—the virtual position where the optical path length in the sample arm equals that of the reference arm. In some cases the mirror image is distorted due to dispersion mismatch in the two arms of the interferometer, causing it to appear blurred. The complex conjugate artifact can lead to ambiguity in image interpretation as well as erroneous analysis of the OCT data.
To avoid the effects of both the central line artifact and the complex conjugate artifact, the zero-delay position is often chosen so that it is located outside of the sample region. Both artifacts can then be removed by using only the positive or negative space. However, ensuring that the zero-delay position is not located within the sample effectively halves the available imaging depth. Data acquisition or processing methods that minimize the effect of the central line and complex conjugate artifacts without needing to keep the zero-delay position outside of the sample area, and therefore allowing double the OCT range, are thus highly desirable. The resulting ability to acquire extended-depth or full-range OCT can be extremely useful for biomedical imaging applications such as imaging of the anterior segment of the eye.
One of the standard methods for minimizing the DC contribution and hence the signal at and near the zero-delay is background subtraction. This can be done by subtracting the signal when no sample is present from the signal acquired with a sample. However, background subtraction alone may be insufficient for minimizing the DC artifact due to ripples in the reference light. Therefore, a method to better minimize the central line artifact is desirable.
Several full-range OCT imaging techniques capable of removing or minimizing the complex conjugate artifact have been demonstrated. Hardware-based approaches to solve this issue have included stepping phase-shifting in the reference arm using piezo-mounted reference mirrors, electro-optic modulators, carrier-frequency shifting methods, quadrature interferometers, and polarization diversity. Hardware-based approaches, however, add cost and complexity of the system, and several approaches have technical limitations. The phase-shifting methods are vulnerable to reduced performance due to inaccuracy in phase shifts (chromatic errors), sample motion, and mechanical instability of the interferometer. Electro-optic and acousto-optic (AO) modulator-based methods add costly components and add complexity for broadband operations. Quadrature interferometers using 3×3 couplers require an additional detection channel, careful calibration, and suffer from wavelength-dependent splitting ratio variations for broadband operations. Polarization diversity methods run into problems due to sample birefringence. There are also some techniques for full-range OCT that use continuously changing phase shifts between densely spaced A-scans. However, subject motion may result in imaging artifacts and reduced performance of complex conjugate suppression.
Other techniques rely on specialized algorithms to reduce or remove the complex conjugate artifact. The majority of these methods require multiple frame acquisitions and heavy post-processing, which make them slower for real-time display and visualization. Hofer et al. demonstrated a dispersion encoded full-range (DEFR) algorithm that uses the dispersion mismatch between sample and reference arm to iteratively suppress complex conjugate artifacts on an A-scan by A-scan basis (B. Hofer et al., “Dispersion encoded full range frequency domain optical coherence tomography,” Opt. Express 17(1): 7-24 (2009) hereby incorporated by reference). While this technique may have favorable application in anterior segment imaging, the algorithm is time-consuming, and requires the sample and reference arm to have a large dispersion mismatch, thereby enforcing additional hardware design-related constraints on the interferometer module. In addition, all of the above mentioned techniques may reduce but not fully minimize the artifact. It would be desirable to have an OCT imaging technique capable of removing or minimizing the complex conjugate artifact without these drawbacks that could be used alone or in combination with other techniques.
The existence of the complex conjugate artifact may lead to failures in analysis algorithms such as tissue layer segmentation. Segmentation of anatomical structures in full-range anterior segment B-scans is crucial for the diagnosis and study of anterior segment diseases. Manual segmentation, however, is subjective and time consuming. It is therefore desirable to have a tissue segmentation algorithm that can be used with full-range OCT images containing complex conjugate artifacts or an otherwise cluttered background; this would be an important step towards faster and reliable quantification.
The ability to segment tissue layers in full-range OCT images with complex conjugate artifacts also enables the application of other algorithms that rely on segmentation, such as thickness analysis and dewarping. In OCT imaging, refraction at the interface of two mediums having different refractive indices can cause image distortions. Refraction-related distortions are especially problematic in anterior segment imaging due to the large difference in the refractive indices of air and corneal tissue (approximately 0.38). The distortions can be corrected using dewarping techniques (V. Westphal et al., “Correction of geometric and refractive distortions in optical coherence tomography applying Fermat's principle,” Opt. Express 10(9): 397-404 (2002)), but correct segmentation of layer interfaces is essential to proper dewarping.